The purpose of this study is to determine whether Fluzone High Dose increases the immune response to the influenza antigens contained in the vaccine compared to standard-dose Fluzone in immunocompromised children and young adults. Safety and efficacy data will also be collected.

Efficacy [ Time Frame: up to 10 months after vaccination ] [ Designated as safety issue: No ]

Gathering data on influenza-like-illness during the influenza season for which the subject was vaccinated in the study. Influenza season typically lasts January through May. Compare rates of diagnosed influenza and rates of reported Influenza Like Illness (ILI) from Questionnaire #2 and also obtained from medical records between the high-dose and standard-dose recipients within each patient group for each influenza season included in the study. We will obtain 3 sets of data related to influenza/ILI and analyze combinations of them.

Diagnosis of ILI (from questionnaire #2). [Centers for Disease Control (CDC) definition of ILI: Fever ≥ 100°F AND cough or sore throat in the absence of another known cause other than influenza for the illness.]

Measure hemagglutinin inhibition (HAI) on blood samples #1 and #2 for all subjects, which is the sample drawn at the "peak" of the immune response. Compare percentage reaching HAI ≥ 1:32 (or 1:40) between the high-dose and standard-dose recipients within each patient group between timepoint 0 (pre-vaccination) and blood draw #2.

Compare proportion of adverse events reported within the 14 days after vaccination by each subject. Compare types and rates of adverse events between the high-dose and standard-dose recipients within each patient group. Subjects will keep a Safety Diary for the 14 days post-vaccination.

Measure HAI on blood samples #1 and #2 for all subjects. Compare percentage reaching a four-fold increase in antibody level between the high-dose and standard-dose recipients within each patient group.

Other immunogenicity [ Time Frame: 10-45 days post-vaccination ] [ Designated as safety issue: No ]

For other immunogenicity: Compare results of blood draw #1 and #2 between the high-dose and standard-dose recipients for each patient group for the following: antibody avidity, microneutralization, T-cell interferon, T-cell IL-2, B-cell Immunoglobulin G (IgG) and B-cell Immunoglobulin A (IgA).

End of season seroprotection [ Time Frame: at least 5 months post vaccination ] [ Designated as safety issue: No ]

Measure HAI on blood sample #3, to be drawn May-September following vaccination. Compare percentage who still have HAI ≥ 1:32 (1:40) between the high-dose and standard-dose recipients within each patient group.

Change in disease status after vaccination [ Time Frame: up to 6 months post-vaccination ] [ Designated as safety issue: No ]

Evaluate disease status changes reported by subject on Questionnaire #2 as well as changes reported in clinic notes over the course of the influenza season. Statistical analysis will compare rates of progress or improvement of disease within the 2 months after vaccination and then within 6 months after vaccination between the high-dose and standard-dose recipients within each patient group.

Will survey subjects at day 30-45 regarding any unplanned health care visit

Will have on-going passive surveillance of adverse events (AEs)/serious adverse events (SAEs) throughout course of influenza season of enrollment. Data collection will stop in September following enrollment.

Rheumatology patients: must be on some type of immunosuppressive or immunomodulatory medication at the time of immunization and considered at least moderately immunosuppressed in the opinion of the primary rheumatologist. Basic guidelines for rheumatology patients: (1) Any patient receiving monoclonal antibody therapy (i.e., infliximab, etanercept, tocilizumab, anakinra) must also be taking another immunosuppressive/immunomodulatory medication; (2) Patients taking steroids as monotherapy must be on a dose of ≥ 2mg/kg/day OR ≥ 20mg/day; (3) Patients on combination therapy where the dose of a single drug may not be very high, but the combination is considered moderately or severely immunosuppressive will be eligible.

Bone Marrow Transplant patients: all patients in clinic eligible

Oncology patients: must be on some type of chemotherapy

Hemodialysis patients: must be on dialysis

Child Health Immunodeficiency Program (CHIP) patients: must have a known diagnosis of HIV

Rheumatology patients: if receiving any of the monoclonal antibodies, etanercept, infliximab, adalimumab, tocilizumab, atlizumab, or anakinra, must also be taking at least one other immunosuppressive/immunomodulatory medication

Unable to come for scheduled follow-up appointments

History of anaphylaxis reaction to influenza vaccination in the past

Severe allergic reaction to any component of the vaccine, including egg protein, or after previous dose of any influenza vaccine

History of Guillain-Barre syndrome ever in the past in the subject or in a parent or a sibling of the subject

Receiving an investigational agent as part of another study or other medical treatment (investigational = not-FDA approved for any indication)

Subject not enrolled in other studies that prohibit him/her from enrolling in this study

Blood draw contraindicated

Pregnancy

Breastfeeding

Received a polysaccharide vaccine (pneumovax) w/in 3 weeks of the vaccination

Absolute neutrophil count (ANC) < 500/uL at the time of vaccination or could potentially have ANC 500/uL during the 5 days after vaccination

Platelet count < 50,000/uL at the time of vaccination

If a subject has a temperature ≥ 100.4°F at the time of enrollment, then the subject must choose to not enroll or delay immunization until afebrile.

Receiving influenza vaccination past December 15 of influenza season.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01685372

Locations

United States, Colorado

Children's Hospital Colorado

Aurora, Colorado, United States, 80045

Sponsors and Collaborators

University of Colorado, Denver

Colorado Clinical & Translational Sciences Institute

Investigators

Principal Investigator:

Donna Curtis, MD, MPH

Children's Hospital Colorado, University of Colorado Denver School of Medicine